Experts Reach Consensus on Detecting Extranodal Extension in HNC Imaging

Head and neck cancer image: © CLIPAREA.com- stock.adobe.comHead and neck cancer image: © CLIPAREA.com- stock.adobe.com

Evidence suggests that extranodal extension (ENE) detected on radiological imaging is a negative prognostic factor in head and neck cancer (HNC). However, until now, criteria to best diagnose ENE and the associated terminology have been ambiguous. Members of the Head & Neck Cancer International Group underwent a yearlong process to harmonize criteria using a 5-stage Delphi process to define the criteria for external extension, and experts from 19 organizations representing 34 countries were included in the consensus. The consensus recommendations are published in The Lancet Oncology.^1,2

“Until recently, we haven’t been using ENE on radiological imaging often and it wasn’t part of routine clinical practice, but in the last few years, because of the advent of transoral robotic surgery, it’s become more common. In the past, everybody was receiving chemoradiotherapy, so it didn’t matter, but now this issue has gradually crept into clinical practice,” Hisham Mehanna, MBChB, PhD, FRCS (ORL) said. Mehanna is chair of head and neck surgery, deputy pro-vice-chancellor of interdisciplinary research, and director of the Department of Head and Neck Studies and Education at the Institute of Cancer and Genomic Sciences at the University of Birmingham in the United Kingdom and lead author of the consensus recommendations.

“We looked at the systematic reviews and found that there was a lot of variability in the literature on ENE,” Mehanna said. However, experts unanimously agreed on several critical criteria for identifying these extensions, emphasizing features such as indistinct or irregular nodal margins, extension into perinodal fat, extension into adjacent lymph nodes, and infiltration into surrounding structures, such as muscle, skin, glands, and the neurovascular bundle.

Conversely, capsular thickening and central nodal necrosis were unanimously deemed inappropriate as diagnostic criteria. “When you get consensus of 80% or more, there’s a strong likelihood that these factors are going to be important and implemented easily,” Mehanna said.

However, the terminology used to describe these extensions sparked less agreement among experts, with longstanding terms such as “matted” and “conglomerate” lacking consensus on their preferred usage. Despite this, there was unified support for using these terms interchangeably in the context of imaging-detected ENE.

“One aspect that surprised us was that radiologists were keen on summary synoptic reporting and [having] a classification system that people can easily report with. So we developed one during the program from the results of the consensus and compared it with 3 widely used classification systems,” Mehanna explained. Again, there was consensus from the participating radiologists to use the new classification, as they found it better than existing ones, he relayed.

“For decades, ENE of tumor cells beyond the lymph node capsule has been recognized as a poor prognostic indicator when identified in pathologic specimens after surgery,” Robert L. Ferris, MD, PhD, FACS explained. “Identifying ENE radiographically has been challenging, as minor levels are difficult to detect on traditional pretreatment CT or MRI. However, extensive ENE has now been demonstrated to be a significant poor prognostic indicator, as shown by Mehanna et al.” Ferris serves as director of the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, professor in the departments of Otolaryngology-Head and Neck Surgery, Immunology, and Radiation Oncology; codirector of the Tumor Microenvironment Center; associate senior vice-chancellor for cancer research; Hillman Professor of Oncology; UPMC senior vice president for oncology programs; and one of the editorial chiefs of this publication.

The validation process is currently underway and includes the same set of radiologists to assess the interrater correlation with using these recommendations and whether it is predictive of outcomes, Mehanna explained. The intent is to bring about consistency by ensuring that the definition of radiological extension is the same internationally.

Moving forward, Mehanna explained that researchers have already begun to discuss how to use the criteria to select patients for clinical studies. For instance, they are discussing whether patients with ENE should receive more treatment and whether those without ENE should receive less treatment. For now, “a set of consensus criteria [are] available in The Lancet Oncology paper that we would recommend they follow, [containing] an easy classification system,” he concluded.

“This advancement will enable the identification of subgroups for whom treatment intensification with additional therapies should be considered and help in identifying genes that contribute to this aggressive disease. Those with radiographic ENE can now be more reliably excluded from treatment deintensification strategies, which might otherwise increase the risk of recurrence or lower survival responses,” Ferris said.

REFERENCES:

1. Henson C, Abou-Foul AK, Yu E, et al. Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations. Lancet Oncol. 2024;25(7):e297-e307. doi:10.1016/s14702045(24)00066-4

2. Abou-Foul AK, Henson C, Chernock RD, et al. Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations. Lancet Oncol. 2024;25(7):e286-e296. doi:10.1016/s1470-2045(24)00143-8